intra-arterial tenecteplase following endovascular thrombectomy for large vessel occlusion stroke

Conditions: Acute Ischemic Stroke

Summary: the purpose of this study is to determine the safety and feasibility of using intra-arterial tenecteplase in patients undergoing blood clot extraction for treatment of acute ischemic (non-bleeding) stroke. intravenous tenecteplase is fda-approved to treat patients with an ischemic stroke presenting within the 0-3-hour time window.

the primary objective of this study is to determine the safety and feasibility of intra-arterial tenecteplase in selected patients with persistent post-thrombectomy hypoperfusion on computed tomography perfusion based on symptomatic intracranial hemorrhage (parenchymal hematoma type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage producing decline from the initial nihss of ≥ 4 points) at 24-36 hours.

Eligibility criteria:
inclusion criteria: * patient/legally authorized representative has signed the informed consent form * ability to comply with the study protocol, in the investigator's judgment * functionally independent (modified rankin scale 0-2) prior to presentation * baseline national institutes of health stroke scale (nihss) ≥ 6 * clinical syndrome consistent with occlusion of the internal carotid artery (ica) or proximal middle cerebral artery (mca), presenting within 4.5- to 24-hours of tlkw * evidence of ica, mca-m1, or mca-m2 occlusion on baseline computed tomography angiogram (cta) or magnetic resonance angiogram (mra). ica/mca tandem occlusions may be enrolled * alberta stroke program early computed tomography score ≥ 6 on pre-thrombectomy unenhanced ct as determined by treating neurologist or reading radiologist * pre-thrombectomy computed tomography perfusion (ctp) or magnetic resonance perfusion (mrp) with core infarction (cerebral blood flow \< 30%) \< 70 ml, mismatch ratio ≥ 1.8, mismatch volume ≥ 15 ml (completed within 120 minutes of skin puncture for thrombectomy) * endovascular thrombectomy of ica, mca-m1 or mca-m2 occlusion performed according to local standard of care, defined as at least completing the initial diagnostic angiogram * ctp performed with rapid ai angioflowtm within 30 minutes of thrombectomy completion * modified thrombolysis in cerebral infarction (mtici) 2b-3 revascularization following endovascular thrombectomy (evt) (or after initial diagnostic angiogram) * presence of tm \> 6 lesion on post-evt ctp of adequate quality for interpretation in the distribution of the symptomatic occlusion exclusion criteria: * current participation in another investigational drug or device study * known hypersensitivity or allergy to any ingredients of tenecteplase * active internal bleeding * known bleeding diathesis (e.g., alzheimer's patients taking lecanemab) * systolic blood pressure \> 185 mm hg or diastolic blood pressure \> 110 mm hg after evt, refractory to medical therapy * known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with inr \> 1.7 * use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban) * treatment with a thrombolytic within the last 3 months prior to randomization * baseline platelet count \< 100,000/mcl (results must be available prior to treatment) * baseline blood glucose \> 400 mg/dl (22.20 mmol/l) * baseline blood glucose \< 50 mg/dl; needs to be normalized prior to randomization * intracranial or intraspinal surgery or trauma within 2 months * intracranial malignant neoplasm, arteriovenous malformation, or unsecured aneurysm \> 1 cm * other serious, advanced, or terminal illness (investigator's judgment) or life expectancy is less than 6 months * history of acute ischemic stroke in the last 90 days * history of hemorrhagic stroke * presumed septic embolus; suspicion of bacterial endocarditis * any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was to be performed * pregnant * acute intracranial hemorrhage on pre-thrombectomy imaging or suspected acute intracranial hemorrhage after evt * acute bilateral strokes on initial imaging * multiple acute intracranial occlusions (except ica/mca) on initial cta or mra * significant hemispheric mass effect or any amount of midline shift due to acute stroke * placement of cervical carotid or intracranial stent during thrombectomy procedure requiring dual antiplatelet therapy

Keywords: brain hemorrhage stroke blood clot